Study of gamma interferon agonists/mimetics

γ干扰素（IFN_（？） 对良好的健康是必需的，特别是通过CD 4 T细胞介导或维持的， 辅助1（Thl）细胞。此外，IFN_1具有直接的抗病毒和抗细胞（抗肿瘤）作用。 活动因此，IFN 1模拟物的发展对免疫系统的免疫调节具有重要意义。 传染病和癌症的治疗。下面列出的具体目标直接测试了 这类模拟物的合理开发以及它们在介导IFN_2中的用途， 活动 1.基于序列和结构相似性的IFN 1肽模拟物的合成 生物活性IFNI，C-末端肽。 2.比较几种细胞内递送IFN_α肽的方法，包括化学方法， 分子表达系统的修饰和应用。 3.确定IFN_i肽模拟物在JAK/STAT活化方面的信号传导功能， 肿瘤抑制基因p21 wAF/cIP上调，neu/HER-2下调 癌细胞中的原癌基因 4.确定IFN_α肽模拟物在抗病毒活性方面的细胞功能， 抗细胞（抗肿瘤）活性和MHC II类分子的上调。 5. IFN_α模拟肽在病毒感染小鼠模型中的生物学活性测定 和癌症

Gamma interferon (IFN_() is an essential cytokine for mediation of functions that are obligatory for good health, particularly that mediated through or maintained through CD4 T- helper 1 (Thl) cells. Further, IFN_, possesses direct antiviral and anticellular (antitumor) activity. Thus, the development of IFN1, mimetics has important implications for immune- therapy in infectious diseases and cancer. The Specific Aims listed below directly test both the rational development of such mimetics as well as their use in the mediation of IFN_, activity. 1. Synthesis of IFN1, peptide mimetics based on sequence and structural similarity to biologically active IFNI, C-terminal peptides. 2. Compare several methods for delivery of IFN_, peptides intracellularly, including chemical modification and use of molecular expression systems. 3. Determine signaling function of IFN_, peptide mimetics in terms of JAK/STAT activation, upregulation of tumor suppressor gene p21 wAF/cIP, and down regulation of neu/HER-2 protooncogene in cancer cells. 4. Determine cellular function of IFN_, peptide mimetics in terms of antiviral activity, anticellular (antitumor) activity, and upregulation of MHC class II molecules. 5. Determine biological activity of IFN_, mimetic peptides in mouse models of virus infection and cancer.